The Neuropathology Core is essential to establish definitive postmortem diagnosis for prospectively enrolled clinical patients, genetic family members, sibpairs and controls. Brains are sectioned and examined according to established protocols. Senile plaques are estimated according to CERAD; neurofibrillary changed staged according to Braak and Braak and NIA-Reagan Instituted criteria applied for diagnosis. Dementia with Lewy bodies is evaluated according to Consensus criteria and Vascular dementia classified according to NINDS-AIREN guidelines. To properly evaluate new diagnostic and treatment modalities and to validate genetic studies, postmortem examination is required to diagnosis and stage AD, evaluate coexisting pathology and to establish other causes of dementia. Although there have been rapid advances in recent years in development of animal models of AD, none fully mimic human disease. Specifically, none exhibit neurofibrillary change which some investigators view as the most significant pathology. Dementia with Lewly bodies account for 20% of dementia cases examined by this Core, but no models exist for Lewy body pathology. Also, there is no adequate model of Vascular dementia. Began in 1985, the Bryan Autopsy Program has changed significantly as the research needs of the Bryan ADRC have evolved. Nevertheless, the Bryan ADRC Autopsy Program remains successful in procuring human tissue as quickly as possible after death. In recent years, a major goal of the Neuropathology Core have been recruited of normal controls. Since 1992, normal controls have been followed with annual neuropsychologic testing and are now coming to autopsy in increasing numbers. The Bryan ADRC Brain Bank is currently a repository of 803 fixed and frozen human brain specimens with detailed neuropathologic examinations and is capable of supplying human tissue to internal investigators as well as to investigators from institutions across the US and worldwide. The Brain Bank serves as a routing service for tissue and data through the Clinical Core and the research projects.